The Fox Chase Cancer Center (FCCC) and the University of Pennsylvania (PENN) Ovarian SPORE is submitted as a partnership between two Philadelphia NCI Cancer Centers requesting support for years 11 through 15 of this SPORE. Over the last 9 years the SPORE program has matured and evolved. Viewing the SPORE today, the notable difference in the new submission has been the recruitment of new and energetic leadership to the SPORE bringing new ideas, technologies, and institutional investment. This translational focus is a benefit of both the SPORE Program's maturity, the depth of research in ovarian cancer at the institutions, as well as nearly unique institutional resources that catalyzed the expansion of the ovarian cancer program at FCCC-PENN. Within the new SPORE are five highly translational Projects. The projects include: PI) Gene Methylation Signatures for Predictive Classification of Response to Therapy;P2) Improving the Estimation and Communication of Ovarian Cancer Risk among BRCA1/2 Carriers to Optimize Decision Making;P3) Therapeutic Micro RNA Strategies for Ovarian Cancer;P4) Targeting Signaling Networks via Novel RNAi Approaches to Improve Therapy for Ovarian Cancer;P5) Advancing T cell Therapy for Ovarian Cancer. The Programs are supported by three separate cores including an Administrative, Biospecimen and Tissue Procurement, and a Biostatistics and Bioinformatics Cores. The SPORE also has a highly effective Career Development Program and a Developmental Pilot Project Program which has been successful at launching the career of many junior investigators and has served to identify new Projects through the first ten years of the SPORE. The investment in the SPORE and the FCCC-PENN Ovarian Cancer Program between 2004 and 2014 comes through direct investments in the SPORE ($6.2 million), with another $10.9 million into the ovarian cancer programs and faculty at PENN and FCCC. In addition, the two NCI Cancer Centers have provided an additional $13.4 million in associated yet important investments supporting the gynecologic oncology clinical and research infrastructure. In addition, over 10 million dollars in collateral and follow on grants have been generated from FCCC-PENN Ovarian SPORE research in the last five years thus bringing the total ovarian cancer (but non-SPORE) investment into the ovarian cancer programs and infrastructure to over 41 million dollars.